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Transcranial ultrasound stimulation of the human motor cortex

Yi Zhang, Liyuan Ren, Kai Liu, Shanbao Tong, Ti-Fei Yuan, Junfeng Sun

iScience 2021, 24, 103429 · 10.1016/j.isci.2021.103429

human healthyhealthyemg mepbehaviour

Abstract

It has been 40 years since the report of long-term synaptic plasticity on the rodent brain. Transcranial ultrasound stimulation (TUS) shows advantages in spatial resolution and penetration depth when compared with electrical or magnetic stimulation. The repetitive TUS (rTUS) can induce cortical excitability alteration on animals, and persistent aftereffects were observed. However, the effects of rTUS on synaptic plasticity in humans remain unelucidated. In the current study, we applied a 15-min rTUS protocol to stimulate left primary motor cortex (l-M1) in 24 male healthy participants. The single-pulsed transcranial magnetic stimulation-evoked motor evoked potential and Stop-signal task was applied to measure the rTUS aftereffects. Here, we report that conditioning the human motor cortex using rTUS may produce long-lasting and statistically significant effects on motor cortex excitability as well as motor behavior, without harmful side effects observed. These findings suggest a considerable potential of rTUS in cortical plasticity modulation and clinical intervention for impulsivity-related disorders.

Abstract via europepmc.

Specieshuman
Subjects24 participants
Sessions per subject1
Randomisedyes
Blindingsingle
Sham / controlinactive transducer
Auditory controldeafened subjects
Readout timingoffline
Anaesthesianot applicable
Readoutsemg mep, behaviourSingle-pulse TMS-evoked motor evoked potential (MEP) amplitude/latency; Stop-signal task (SSRT, GoRT, SSD, trial accuracy)
Direction of effectexcitatoryActive-rTUS potentiated MEP amplitude for at least 30 min post-intervention and significantly reduced stop-signal reaction time (improved motor inhibitory control) compared with baseline, whereas sham-rTUS produced no significant change in either measure.
Adverse eventsnone observedNo participants reported side effects (headache, neck pain, scalp pain, itch, burning, mood changes) after either active- or sham-rTUS; simulated/measured intensities and MI were below FDA diagnostic ultrasound limits and simulated temperature increases were <0.2 degrees C.

Exposures

Exposure 1: rTUS to left primary motor cortex (l-M1)

Target: primary motor cortex — “left primary motor cortex (l-M1)
Device: Olympus / Panametrics · Olympus NDT · V391-SU

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper)
Pulse repetition frequency (Hz)100✓✓
Duty cycle (%)5✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)8.05✓✓
Free-field Ispta (W/cm²)0.403✓✓
In-situ estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)2.85✓✓
In-situ Ispta (W/cm²)0.142✓✓
Pressure, domain unspecified (kPa)419✓✓
Protocol, in the paper’s words

A 15-minute rTUS session (or sham) was delivered to l-M1 with inter-stimulus interval ISI=8 s and 50 tone-bursts (NTB) per sonication train of 500 ms; total on-state duration of ultrasound across the 15-min session was 2.647-2.657 s. In the sham condition the output of the TUS system was turned off. Sessions (active/sham) were delivered in a crossover design with >7 days washout.

Flags from extraction

  • exposures[0].timing.pulse_duration_msPaper states tone-burst-duration (TBD)=500 ms, identical to the stated sonication duration (SD)=500 ms; duty cycle (5%) divided by PRF (100 Hz) implies an individual burst duration of 0.5 ms, suggesting TBD may be a units typo (500 microseconds). Recorded as stated (500) per the burst rule.
  • exposures[0].unspecified_domain.pressure_kpa419 kPa is given as the simulation source/target driving pressure; unclear whether this corresponds to a free-field or in-situ (at-target) domain, so placed in unspecified_domain.
  • auditory_controlNo masking sound was used; authors instead selected a transducer/coupler reported to produce no perceivable vibration or sound and had subjects wear earplugs, and argue auditory confound is unlikely; does not map cleanly onto the closed vocabulary.